Fox Fordyce Disease

NORD gratefully acknowledges Timothy H. McCalmont, MD, Departments of Pathology and Dermatology, University of California, San Francisco, for assistance in the preparation of this report.

Synonyms of Fox Fordyce Disease

apocrine duct occlusion

apocrine miliaria

General Discussion

Fox-Fordyce disease is a rare skin disorder that primarily affects women. The disorder is characterized by intense itching especially in the underarm area, the pubic area and around the nipples. In Fox-Fordyce disease abnormalities affecting the apocrine sweat glands causes inflammation, and enlargement of the glands and the characteristic intense itching. Skin near an affected area may become darkened and dry and multiple, small, raised bumps (papules) may develop. Hair follicles in the affected area can become secondarily damaged, resulting in hair loss. The exact cause of Fox-Fordyce disease is unknown.

Signs & Symptoms

The symptoms of Fox-Fordyce disease may appear suddenly usually following conditions of heat, humidity or friction. The disease is characterized by an eruption of multiple, small, raised bumps on the skin near the apocrine glands.

The apocrine glands are specialized sweat glands that play a pheromonic role in animals; a similar role has been postulated in humans. Pheromones are chemicals secreted by animals that influence social or sexual behavior of other animals of that species. Apocrine glands respond to sex and stress stimuli. Apocrine glands become extremely active during puberty. Most apocrine glands are found in the armpits or the groin. They may also be found by the nipples, external ear canal, eyelids, and around the bellybutton.

The papules are usually skin-colored, but may be yellowish or reddish in color. They are usually dome-shaped and smooth. Affected areas usually have many small papules. Papules are most often found in the armpits (axillae). The affected areas are often extremely itchy (pruritus) and sweating in these areas may also be absent (anhidrosis). Itching may be mild or may be severe enough to disturb sleep. Hairs within follicles in the affected area may fall out.

Causes

The exact cause of Fox-Fordyce disease is unknown. Researchers have speculated that obstruction of the apocrine gland ducts is necessary for the development of Fox-Fordyce disease, but studies have not been able to definitely confirm this theory. Researchers speculate that blocked ducts rupture causing inflammation where the duct comes close to the hair follicle. The inflammatory reaction around hair follicles includes specialized leukocytes (white blood cells) that engulf extruded secretory debris.

Researchers have also speculated that additional factors such as hormonal or genetic ones may play a role in the development of Fox-Fordyce disease. However, research into the cause(s) of Fox-Fordyce disease has not yielded any definitive answers as yet. More research is necessary to determine the exact cause of Fox-Fordyce disease.

Affected Populations

Fox-Fordyce disease occurs primarily in women between 13 and 35 years of age. However, in rare cases, it can affect men and children and women who are post-menopausal. Some reports place the ration of affected women to men at 9:1. The incidence of Fox-Fordyce disease is unknown. Heat, humidity, stress and exercise have been noted as exacerbating factors. In addition, Fox-Fordyce disease may be more severe during menstruation and tends to disappear (spontaneously resolve) during pregnancy. Fox-Fordyce disease was first described in the medical literature in 1902.

Related Disorders

Symptoms of the following disorders can be similar to those of Fox-Fordyce disease. Comparisons may be useful for a differential diagnosis.

Hidradenitis suppurativa is a chronic, pus-producing (suppurative), scarring (cicatricial) disease process that occurs due to obstruction of hair follicles and secondary infection and inflammation of certain sweat glands (apocrine glands), particularly those under the arms (axillae) or within the anal/genital (anogenital) region. The disease is characterized by the development of recurrent, boil-like nodular lesions and deep pus-containing pockets of infection (abscesses) that may eventually rupture through the skin. Healing of affected areas is typically associated with progressive scarring (fibrosis). The specific underlying cause of hidradentitis suppurativa is unknown. (For more information on this disorder, choose “hidradentitis suppurativa” as your search term in the Rare Disease Database.)

Keratosis follicularis, also known as Darier disease, is a rare, genetic skin disorder. Affected individuals develop skin lesions that consist of thickened, rough bumps (papules) or plaques that may also be greasy or have a brown or yellow crust. These hardened, scaly lesions are progressive and may gradually grow bigger or spread. The nails and mucous membranes are also affected in many cases. Additional symptoms may be present in some cases. Individuals may have periods of time when signs improve (remission), but the lesions usually recur (relapse). The specific problems vary from one individual to another. Keratosis follicularis is inherited as an autosomal dominant trait. (For more information on this disorder, choose “keratosis follicularis” as your search term in the Rare Disease Database.)

Hailey-Hailey disease is a rare genetic disorder that is characterized by blisters and lesions most often affecting the neck, armpits, skin folds and genitals. The lesions may come and go and usually heal without scarring. Heat, sweating and friction often aggravate the disorder. The symptoms of Hailey-Hailey disease occur because of the failure of skin cells to stick together resulting in the breakdown of affected skin layers. Hailey-Hailey disease occurs due to a mutation in a specific gene that creates a protein that is essential for the proper health of skin. The disorder becomes apparent after puberty, usually by the third or fourth decade, but symptoms can develop at any age. (For more information on this disorder, choose “Hailey-Hailey” as your search term in the Rare Disease Database.)

Miliaria is a common occurrence and is usually known as “heat rash”. The sweat gland is blocked and fluid is trapped in the surrounding area. There are various types. However, they do not involve the hair follicle and do not result in hair loss. Cooling the patient with water or compresses or putting them in a cooler place usually results in the disappearance of the rash.

Diagnosis

A diagnosis of Fox-Fordyce disease is made based upon identification of characteristic symptoms (i.e., papular eruptions on apocrine gland areas), a detailed patient history, and a thorough clinical evaluation. Surgical removal and microscopic evaluation (biopsy) of affected tissue may be useful in obtaining a diagnosis. An experienced dermatopathologist will be necessary to correctly diagnose the disease from a biopsy.

Standard Therapies

Treatment

The treatment of Fox-Fordyce disease is directed toward the specific symptoms that are apparent in each individual. Consultation with a dermatologist is recommended. Specific therapies that have been used include estrogen hormones, oral retinoids, steroid creams, and topical antibiotics. No therapy is universally effective in all patients.

Estrogen hormones, usually given as part of estrogen-based oral contraceptives, have been most effective in treating women with Fox-Fordyce disease. Less effective therapies include oral retinoids (such as tretinoin), corticosteroid creams and topical antibiotics (such as clindamycin) have been beneficial in some cases while ineffective in others. Some of these therapies may be associated with irritation, limiting their ability to be used a long-term therapy.

Some women with Fox-Fordyce disease see a significant improvement or resolution of the disease during pregnancy.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

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